Team "Personalized medicine, pharmacogenomics, therapeutic optimization", Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France.
Institut du Cancer Paris CARPEM, APHP, Gastroenterology and Gastrointestinal Oncology Department, APHP.Centre - Université Paris Cité, Hôpital Européen G. Pompidou, Paris, France.
Clin Cancer Res. 2024 Jun 3;30(11):2351-2358. doi: 10.1158/1078-0432.CCR-23-3964.
Over the past decade, our understanding of the diversity of colorectal cancer has expanded significantly, raising hopes of tailoring treatments more precisely for individual patients. A key achievement in this direction was the establishment of the consensus molecular classification, particularly identifying the challenging consensus molecular subtype (CMS) CMS4 associated with poor prognosis. Because of its aggressive nature, extensive research is dedicated to the CMS4 subgroup. Recent years have unveiled molecular and microenvironmental features at the tissue level specific to CMS4 colorectal cancer. This has paved the way for mechanistic studies and the development of preclinical models. Simultaneously, efforts have been made to easily identify patients with CMS4 colorectal cancer. Reassessing clinical trial results through the CMS classification lens has improved our understanding of the therapeutic challenges linked to this subtype. Exploration of the biology of CMS4 colorectal cancer is yielding potential biomarkers and novel treatment approaches. This overview aims to provide insights into the clinico-biological characteristics of the CMS4 subgroup, the molecular pathways driving this subtype, and available diagnostic options. We also emphasize the therapeutic challenges associated with this subtype, offering potential explanations. Finally, we summarize the current tailored treatments for CMS4 colorectal cancer emerging from fundamental and preclinical studies.
在过去的十年中，我们对结直肠癌的多样性的理解有了显著的提高，这为为个体患者量身定制更精确的治疗方案带来了希望。在这方面的一个重要成就是共识分子分类的建立，特别是确定了具有挑战性的共识分子亚型（CMS）CMS4，其与预后不良相关。由于其侵袭性，广泛的研究致力于 CMS4 亚组。近年来，在组织水平上揭示了特定于 CMS4 结直肠癌的分子和微环境特征。这为机制研究和临床前模型的发展铺平了道路。同时，还努力识别 CMS4 结直肠癌患者。通过 CMS 分类镜头重新评估临床试验结果，提高了我们对该亚型相关治疗挑战的理解。对 CMS4 结直肠癌生物学的探索产生了潜在的生物标志物和新的治疗方法。本综述旨在提供对 CMS4 亚组的临床生物学特征、驱动该亚型的分子途径以及可用的诊断选择的深入了解。我们还强调了与该亚型相关的治疗挑战，并提供了潜在的解释。最后，我们总结了从基础和临床前研究中出现的针对 CMS4 结直肠癌的针对性治疗方法。
